Acylation of diarylguanidine salts of diamino dibenzothiophenedioxide sulfonic acids



Patented Nov. 25, 1952 ACYLATION OF DIARYLGUANIDINE SALTS OF DIAMINO'DIBENZOTHIOPHENEDIOX- IDE SULFONIC ACIDS Hans Z. Lecher, Plainfield,and Dale R. 'Eberhart, Bound Brook, N. J., assignors to AmericanCyanamicl Company, New York, N. Y., a corporation of Maine No Drawing.Original application April 4, 1950,

Serial No. 153,992. Divided and this application April 26, 1951; SerialNo. 223,174

'7 Claims.

The present invention relates to the acylation of aminosulfonic acids.More particularly, it is concerned with the acylation of aminosulfonicacids of the dibenzothiophenedioxide series. Specifically, this case isconcerned with the acylation of diarylguanidine salts of those acids. Assuch this application is a division of our application for United StatesLetters Patent, Serial No. 153,992, filed April l, 1950.

Many of these compounds possess marked fluorescent properties and areparticularly useful to overcome the yellowish cast which is caused byvarious factors in many diiierent white materials, especially cellulosicfabrics. These compounds, however, are not claimed per se in the presentapplication. They form in part the subject matter of the copendingapplications of Scalera and Eberhart for United States Letters Patent,Serial No. 45,425, filed August 20, 1948; and Serial No. 168,392, filedJune 15, 1950.

Despite their desirability in use, the commercial exploitation of thesematerials has been hampered by the lack of a generally suitableacylation method of preparing them. It has been found that the knownmethods of acylation are not suitable for industrial development when anattempt is made to apply them to these materials. Many difiiculties areencountered.

For example, while many amino compounds are readily acylated with acidhalides in aqueous solution,3,7-diaminodibenzothiophenedioxide-2,3-disulfonic acid, cannot beacylated at all in this way. Attempted reaction gives little or none ofthe desired product, the acid halide instead being mostly destroyed byhydrolysis. In still other cases, where the halide may not be quite sosensitive, and is not destroyed so rapidly or completely, the resultsare unsatisfactory for other reasons.

Non-polar organic solvents have been used successfully in many similartypes of acylations. However, they have not been utilized with theseaminosulfonic acids. Neither the free acids nor their metal salts can besatisfactorily acylated in an organic medium. Their solubility is toolow. Further, the amino groups of the free acid are renderedcomparatively inert to acylation under these conditions. This appears tobe due to association With the sulionic acid groups in Zwitter ion formwhich appears to resist the action of the acyl halide.

If these difficulties could be successfully overcome, there would exista demand for both the successful procedure and its products. It is,

therefore, the principal object of the present invention to devise anacylation method suitable for use with these compounds for which theknown procedures were not satisfactory.

In general, the object of the present invention has been accomplished bycarrying out the reac tion in a non-polar solvent with certain organicbase salts of the amino sulfonic acids. In view of the diflicultiesencountered in the past, the effectiveness of the process of the presentinvention is particularly surprising, especially with those compounds,such as alkoxy-substituted benzoyl halides, that are exceptionallydificult to use because of their unusual sensitivity. In all cases, theproducts are obtained in satisfactory quality and yield.

The use of these organic base salts, in place of the free acids or theiralkali metal salts, apparently has the effect of breaking up the stableZwitter ion structure of the aminosulfonic acid, and of enhancing thesolubility in the solvent. In any case, the desired acylation isaccomplished by converting the aminosulfonic acid to its salt with theorganic base and treating the resultant salt with the acyl halide in anon-polar solvent.

In accordance with the present invention, symmetrical diaryl guanidineshave been found very suitable for this salt formation. They readily formwell-defined crystallizable salts with the dibenzothiophene dioxideaminosulfonic acids of the present invention. These salts are smoothlyacylated in organic solvents. After acylaticn is complete, the reactionmixture is made alkaline, breaking down the diaryl guanidine salt of theproduct. A particularly useful solvent is nitrobenzene, permitting aneasy recovery of both the reaction product and the diarylguanidine. Thereaction product is made alkaline with an organic alkali salt, forexample sodium acetate, potassium propionate, sodium ethylate, sodiumphenoxide, sodium lactate, potassium p-chlorophenoxide, and the like.The nitrobenzene retains the diaryl guanidine in solution and permitsits removal with the organic solvent; the acylated sulfonic acid is outof solution as the alkali salt and can be isolated by known methods.

While .a wide variety of aminosulfonic acids may be acylated by themethod of the present invention, it is particularly applicable to theaminosulfonic acids of the dibenzothiophene series, such as3,7-diarninodibenzothiophenedioxide-2,8-disulionic acid and its alkyland chloro derivatives.

A wide variety of symmetrical diaryl substituted guanidines can be usedsuccessfully in the process of the present invention. Among these may beincluded diphenylguanidine, phenyl-opresent invention. It is essentialthat they have solvent action on the product and that they be stable tothe reactants. In general, organic solvents boiling above about 120degrees C. are to be preferred. Suitable solvents include both aliphaticand aromatic hydrocarbons and their halogeno and nitro derivatives, aswell as esters, ethers, and ketones. By way of specific example, thefollowing solvents are effective: monoand dichlorobenzene and thechlorotoluenes; the xylenes; nitrobenzene and the nitrotoluenes; cymene,acetylene tetrachloride, acetophenone, cyclohexanone, and anisole.

It is an advantage of the present invention that the salts can beprepared by any suitable method. For example, the aminosulfonic acid canbe dissolved in water, neutralized, and treated in aqueous solution witha soluble salt of the guanidine. The desired salt crystallizes directlyfrom the solution. It is not necessary for the purpose of this inventionthat the salt be strictly pure or dry. It is dispersed in the selectedorganic solvent. A convenient practice at this point is to remove anywater present by distilling a part of the solvent. Acylation is thenreadily efiected by adding the acyl halide to the mixture.

A suitable acyl halide may be selected from a wide variety of aliphaticand aromatic carboxylic acids. These include, for example, benzoylchloride and its alkylated, nitrated, and halogenated derivatives;butyryl chloride, ethanesulfonyl chloride, chloroacetyl chloride,crotonyl chloride, propionyl bromide, p-toluenesulfonyl chloride,thiophene-Z-carboxylic acid chloride, alphanaphthoyl chloride,2-hydroxy-3-naphthoyl chloride, benzoyl bromide, nicotinyl chloride andacetylsulfanilyl chloride, as well as such bifunctional compounds asterephthaloyl chloride, succinoyl chloride, and adipoyl chloride. As hasbeen mentioned, the process of the present invention is particularlyuseful in utilizing the acid chlorides of alkoxy-substituted benzoicacids, such as the isomeric anisoyl chlorides, o-ethoxybenzoyl chloride,o-propyloxybenzoyl chloride, and 2,4- and 2,5-dimethoxy benzoylchlorides.

Example 1 NaSO3 SOaNa C5l OONH- S NHCOC@H5 On A solution is preparedfrom 26.3 parts of di-otolylguanidine, 11.9 parts of concentratedhydrochloric acid, and water to the volume of 200 parts of water. Thisis slowly added to a solution prepared by adding 20.3 parts of3,7-diaminodibenzothiophenedioxide 2,8-disulfonic acid to 100 parts ofwater, neutralizing with 5 N sodium hydroxide solution, and diluting tothe volume of 200 parts of water. The salt which crystallizes out isfiltered, washed, and dried.

NaSOz- A mixture of 7.2 parts of benzoyl chloride, 50 parts ofchlorobenzene, and 4.4 parts of the above prepared di-o-tolylguanidinesalt is gradually heated. Condensation begins at about degrees C., asevidenced by hydrogen chloride evolution, and is complete at reflux. Thereaction mixture is then cooled, and neutralized by the addition of 11.3parts of phenol in 29 parts of 5 N sodium hydroxide solution. Theproduct is stirred, filtered and washed with nitrobenzene. It is thenslurried in water and salt, boiled to remove traces of nitrobenzene,cooled, filtered, washed and dried.

The di-o-tolylguanidine is retained in the nitrobenzene solution and isreadily recovered for re-use by steam distillation to remove thenitrobenzene.

Example 2 NaSOa- SO3I\'u CGHSCHZCHCONH- NHCOCH=CHC5H5 A mixture of 24parts of nitrobenzene and 4.4 parts of the di-o-tolylguanidine salt,prepared as described in Example 1, is heated to 120 degrees C. andtreated with 2.5 parts of cinnamoyl chloride. The mixture is then heatedfurther to degrees C. to complete the reaction, cooled to 85 degrees C.,and treated with a solution of 1.9 parts of phenol in 5 parts of 5 Nsodium hydroxide. The resulting bright yellow precipitate is filtered,washed with nitrobenzene and acetone and dried.

Example 3 The di-o-tolylguanidine salt of3,7-diaminodibenzothiophenedioxide 2,8-disulfonic acid is preparedaccording to the procedure described in Example 1. This salt (8.8 parts)is heated at degrees C. in 48 parts of nitrobenzene with 8.3 parts of2,4-diethoxybenzoyl chloride until a test for primary amino groupsbecomes negative. The resulting mixture is treated at 148-50 degrees C.with 8.0 parts of finely powdered anhydrous sodium acetate. After beingstirred approximately two hours at this temperature, the mixture iscooled, filtered, and washed with 48 parts of nitrobenzene. The productis slurried in water, freed of nitrobenzene by steaming, filtered anddried.

Example 4 The acylation reaction of Example 3 is repeated. The reactedmixture is cooled to 70 degrees 80 degrees C. and treated with asolution of eight parts of 5 N sodium hydroxide solution in eight partsof alcohol. The rest of the product is worked up as in Example 3, andresults in an excellent yield of very pure product.

Example 5 Example 3 is repeated substituting for the di-o-tolylguanidinesalt in that procedure 8.5 parts of the corresponding diphenylguanidinesalt, prepared by adding an aqueous solution of diphenylguanidinehydrochloride to the sodium salt of 3,'7-diaminodibenzothiophenedioxide2,8- disulfonic acid. On working up the product as in Example 3 anexcellent yield of suitably pure product is obtained.

Example 6 SOaNa 6 A solution of 20.7 parts of p-hydroxybenzoic stitutinganiline for morpholine in the above acid in 100 parts of watercontaining 12 parts of procedure. sodium hydroxide, is gradually treatedat 25 While the foregoing examples produce sodium degrees C. with 84.4parts of p-toluenesulfonyl salts rather than free acids, this does notinterchloride. Alkalinity is maintained by the simul- 5 fere withutilization of the product. The salts taneous addition of approximately2.4 additional may be converted to the acids and vice versa by parts ofsodium hydroxide. The product is then any or" the usual methods. Theother alkali precipitated with acetic acid, filtered, washed, metal andammonium salts may be prepared and dried at 60 degrees C. 5.8 parts ofthe from the acid. In any case, since the compounds p-tosyloxybenzoicacid, thus prepared is con- 10 will be most often employed with soap orother verted to acid chloride in the usual way with 3.6 alkalinematerials, it makes little diiference parts of thionyl chloride. Excessthionyl chloride whether a salt or the acid is the starting mateisremoved in a stream of air. 2.5 parts of the rial, since the free acidwill probably be conresulting acid chloride is added at 80 degrees C.verted to a salt in that use.

to 12 parts of nitrobenzene containing 2.2 parts 5 We claim:

of he di-0 1y e n Salt prepared as in 1. The method of acylating asulfonic acid Example 1. The reaction is completed at 240 of3,7-diaminodibenzothiophenedioxide, which degrees C., the mixture thenbeing cooled to 75 comprises heating a mixture comprising a symdegreesC. and neutralized with a solution of metrical-diarylguanidine salt ofthe selected 0.59% part of phenol in 2 parts of 5 N sodium aminosulfonicacid, an acid halide, and an inert hydroxide solution. The product isfiltered, organic solvent. washed with nitrobenzene followed by acetone,2. A process according to claim 1 in which, and dried at 110 degrees C.after completion of the reaction, the product is Example 7 NaSO3 someooNn- \S/ -NH( :0 02

0 CH3 o CH3 15.2 parts of p-anisic acid is added gradually precipitatedby treatment with an alkalineto 58 parts of chlorosulfonic acid at 5-11degrees reacting organic metal salt. C. After one-half hour the mixtureis gradually 3. A process according to claim 1 in which the warmed to'75 degrees C. and maintained at this organic solvent is nitrobenzene.temperature one hour. It is then cooled, drowned 40 4. A processaccording to claim 1 in which the in ice, and filtered. 2.9 parts of theresulting symmetrical diarylguanidine is symmetrical sulfonyl chlorideis treated with 8 parts of mordiphenylguanidine. pholine. The reactionmixture is slowly treated 5. A process according to claim 1 in which thewith 5 N sodium hydroxide, the temperature acid halide is an aroylchloride. rising to 25 degrees C. After acidification with 6. A processaccording to claim 5 in which the hydrochloric acid, the2-methoxy-5-carboxyaroyl chloride is an alkoxy-substituted benzoylbenzene sulfonyl morpholine is filtered. It melts chloride. at 218-219degrees C. 7. A process according to claim 1 in which the 2.6 parts ofthis product is converted to the symmetrical diarylguanidine issymmetrical dicorresponding carboxylic acid chloride bytreato-tolylguanidine. ment with 1.6 parts of thionyl chloride, in theHANS Z. LECHER. usual manner. This is then added to a mixture DALE R.EBERHART. of 12 parts of nitrobenzene and 2.2 parts of thedi-o-tolylguanidine salt prepared in Example 1. REFERENCES $171733 Aftertwenty minutes at 14.0 degrees-145 degre The following references are ofrecord in the C., the mixture is treated with a solution of 0.9 m of tpatent:

part of phenol in 2 parts of 5 N sodium hydroxide, m I

with immediate formation of a yellow precipitate. UNITED STALES PATENTSThe product is filtered hot, washed with nitro- Number Name Date benzenefollowed by acetone, and dried. 50 2,563,493 Scalera Aug. 7, 1951 Theanalogous disulfonanilide, which has sim- 2,563,795 Scalera Aug. '7,1951 ilar properties, is obtained in a similar Way, sub-

1. THE METHOD OF ACYLATING A SULFONIC ACID OF3,7-DIAMINODIBENZOTHIOPHENEDIOXIDE, WHICH COMPRISES HEATING A MIXTURECOMPRISING A SYMMETRICAL-DIARYLGUANIDINE SALT OF THE SELECTEDAMINOSULFONIC ACID, AN ACID HALIDE, AND AN INERT ORGANIC SOLVENT